Clin Exp Vaccine Res.  2012 Jul;1(1):50-63. 10.7774/cevr.2012.1.1.50.

Mucosal vaccine adjuvants update

• Rhee JH
• Lee SE
• Kim SY

• KMID: 2278788
• DOI: http://doi.org/10.7774/cevr.2012.1.1.50

Abstract

Mucosal vaccination, capable of inducing protective immune responses both in the mucosal and systemic immune compartments, has many advantages and is regarded as a blue ocean in the vaccine industry. Mucosal vaccines can offer lower costs, better accessability, needle-free delivery, and higher capacity of mass immunizations during pandemics. However, only very limited number of mucosal vaccines was approved for human use in the market yet. Generally, induction of immune responses following mucosal immunization requires the co-administration of appropriate adjuvants that can initiate and support the effective collaboration between innate and adaptive immunity. Classically, adjuvant researches were rather empirical than keenly scientific. However, during last several years, fundamental scientific achievements in innate immunity have been translated into the development of new mucosal adjuvants. This review focuses on recent developments in the concepts of adjuvants and innate immunity, mucosal immunity with special interest of vaccine development, and basic and applied researches in mucosal adjuvant.

Keyword

Mucosal; Vaccine; Adjuvant; Innate immunity

MeSH Terms

Achievement
Adaptive Immunity
Cooperative Behavior
Humans
Immunity, Innate
Immunity, Mucosal
Immunization
Mass Vaccination
Pandemics
Vaccination
Vaccines
Vaccines

Figure

• 

  Fig. 1 The target site of vaccine adjuvants. Most of the recently developed specific adjuvants, such as pattern recognition receptor (PRR) ligands act on signal 0 (antigen recognition and antigen-presenting cells [APCs] activation), and indirectly on signal 2 (co-stimulation). In addition, PRR ligands can act on signal 1 (efficient presentation of the co-administered antigen). Modified from Guy [12].

• 

  Fig. 2 Pattern recognition receptor (PRR) and signaling (A) Toll-like receptors (TLRs). TLR receptors recognize different microbial associated molecular patterns: the heterodimer of TLR4 and MD-2 recognizes lipopolysaccharide (LPS); TLR2 recognizes triacyl and diacyl portions of lipoproteins together with TLR1 or TLR6, respectively; TLR5 recognizes flagellin; TLR3 recognizes double-stranded RNA; TLR7 recognizes single-stranded RNA and TLR9 recognizes bacterial and viral DNA, the so-called CpG DNA. The signaling pathways of TLRs are mediated by selective usage of adaptor molecules, MyD88, Toll-receptor-associated activator of interferon (TRIF), TIR-associated protein (TIRAP) and Toll-receptor-associated molecule (TRAM). (B) C-type lectins (CLRs), retinoic acid-inducible gene-like receptors (RLRs) and nucleotide binding domain (NOD)-like receptors (NLRs). CLRs recognize carbohydrates on microorganisms via the carbohydrate-binding domain. Dectin-1 is well studied. RLRs are composed of two N-terminal caspase-recruitment domains (CARDs), a central DEAD box helicase/ATPase domain, and a C-terminal regulatory domain (RD). They are localized in the cytoplasm and recognize the genomic RNA of dsRNA viruses, and dsRNA generated as the replication intermediate of ssRNA viruses. RLRs interact with IPS1 via their CARD domains, resulting in type 1 interferon production through IkB kinase, inducible (IKKi)/TANK-binding kinase 1 (TBK1). NLRs are composed of a central NOD and C-terminal leucine-rich repeats (LRRs). NODs activate caspase-1, resulting in processing of pro-interleukin-1β (IL-1β) to mature IL-1β. ASC, apoptosis-associated speck-like protein; IFN, interferon; IPS1, IFN-β promoter stimulator 1; IRF, interferon regulatory factor; MDA-5, melanoma-differentiation-associated gene 5; NF-kB, nuclear factor-kB; NLPR3, NLR family, pyrin domain-containing 3; RIG-1, retinoic acid-inducible gene I. Modified from Akira [15].

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